The Agricultural Health Study (AHS) is a long-term prospective study of potential health effects associated with exposure to pesticides and other agricultural exposures. The study is a collaboration of the National Cancer Institute, the National Institute of Environmental Health Sciences, and the US Environmental Protection Agency, with additional collaboration by the National Institute for Occupational Safety and Health. We are examining cancer incidence and other health endpoints in a prospective study of licensed pesticide applicators, spouses and children from North Carolina (NC) and Iowa (IA). Over a 3-year period (1993-7), we enrolled more than 57,000 licensed applicators, representing 82% of eligible private pesticide applicators (largely farmers) in IA and NC and 43% of commercial applicators from Iowa. About 40% of the private applicators also completed a more detailed take-home questionnaire covering farming practices and health. Nearly 32,000 spouses of farmer applicators enrolled and 2/3 of these also provided data on reproductive health, including information on all children under age 21. Since enrollment, 70% of participants completed the five-year followup phone interview (1999-2003) and the study is on track to achieve a similar response rate in our current followup phone interview. Annually, cancer incidence among the applicators, spouses, and children is determined through linkage with the population-based cancer registries in IA and NC. Follow-up computer-assisted telephone interviews are used to update exposure information, identify cases of non-malignant disease, and to collect information on changes in health status since enrollment in the study. We are currently completing the second round of followup with cohort members. Buccal-cell samples have been collected from participants in order to extract DNA for future analyses of gene and environment interactions. In addition, a dietary assessment (food frequency questionnaire) was self-completed and returned by mail. In-depth assessment of agricultural exposures has been done for a small sample of farmers and their families in order to validate the questionnaires and facilitate exposure classification. Both environmental and biological samples were collected. Non-cancer outcomes of particular interest in this follow-up period include neurological diseases and symptoms (Parkinson's Disease, hearing loss, depression, and neurobehavioral function), respiratory and allergic outcomes (asthma, rhinitis, chronic bronchitis, respiratory mortality), heart attacks (incidence and mortality), diabetes (both gestational and in adults), autoimmune diseases (rheumatoid arthritis), age-related macular degeneration, and reproductive outcomes (fertility, birthweight, pre-eclampsia, spontaneous abortion) in addition to cancer. We are currently involved in a number of substudies to collect more detailed information on potential health consequences of pesticides. The Growth and Puberty (GAP) Study is an intramurally-funded pilot study to assess the feasibility of measuring early puberty markers (hormone levels in urine and saliva, height velocity, Tanner staging) among farm children in the AHS. This study has enrolled approximately 60 children and the last of the three home visits will be completed by December 2008. The Genes and Age Related Macular Degeneration (GENARM) Study is obtaining medical records, opthamalogical photographs, and saliva as a source of DNA for individuals who reported incident macular degeneration at one of the followup interviews. Field work is completed and data analysis is ongoing. In a collaboration with Frederic Gerr at the University of IA, we conducted a study of neurobehavioral function using a number of standardized tests. Over 700 farmers participated and we are currently analyzing specimens for paraoxonase activity and genes related to organophosphate metabolism. Two more (Parkinson's disease and lung health) are described in separate annual reports. Recent results from the Agricultural Health Study include: 1) Significant association of allergic asthma in adults with pesticide use, particularly organophosphate insecticides which have been shown in animal models to increase allergic airway responsiveness, 2) significant association with pesticides and rhinitis among commercial pesticide applicators with a dose-response relationship for users of both 2,4-D and glyphosate (common herbicides), and 3) no association with heart attack mortality and morbidity with pesticide use. We continue to analyze data on farm exposures and non-cancer morbidity. Ongoing work focuses on allergic and respiratory outcomes, reproductive outcomes, endocrine disorders, and neurological outcomes. Rhinitis is a common symptom among farmers and has been shown to be predictive of future respiratory disease;we are currently evaluating whether pesticide use is associated with rhinitis among farmers. Analyses of reproductive outcomes continues and focuses on preeclampsia and use of pesticides during pregnancy as well as other adverse pregnancy and birth outcomes, uterine fibroids, and infertility. We are currently evaluating thyroid disease among farm women and plan to assess incident diabetes in women in the coming year. Recent work also focuses on mortality in the cohort, indicating elevated injury mortality common among farmers, but also increased risk of specific cancer mortality. Follow-up telephone interviews are being conducted and will be completed in FY2010. We are currently conducting validation studies of self-reported ALS and macular degeneration and are planning for validation of self-reported disease outcomes for Parkinson's disease, stroke, and rheumatoid arthritis.